Metabolic syndrome is characterized by an increase in central adiposity, abnormal lipid profile, elevated blood pressure, and insulin resistance, all of which may contribute to the development of cardiovascular disease. Metabolic syndrome is a major public health problem. The prevalence of metabolic syndrome is increasing and the syndrome is estimated to affect approximately 60 million Americans, or about 20-30% of the American population. Metabolic syndrome is a state of insulin resistance and chronic inflammation, as reflected by elevated levels of inflammatory adipocytokines, including TNF-alpha and IL-6 which contribute to increase C-reactive protein (CRP), endothelial dysfunction and cardiovascular disease. Patients with metabolic syndrome present with increased abdominal adiposity and therefore may have reduced growth hormone (GH) levels. GH deficiency (GHD) may contribute independently to increased cardiovascular risk through effects on insulin resistance, inflammatory markers and other mechanisms. Despite data suggesting that relative GH deficiency is prevalent in viscerally obese patients and increasing data suggesting a link between GH deficiency and cardiovascular disease, the prevalence and contributions of GH deficiency to cardiovascular disease in the metabolic syndrome is not known. In this grant we will determine the prevalence of GH deficiency in the metabolic syndrome, and the contribution of GH deficiency to increased IMT and endothelial dysfunction, markers of cardiovascular disease. Based on preliminary data, we hypothesize that growth hormone (GH) levels are reduced in metabolic syndrome in association with excess visceral adiposity and that among patients with metabolic syndrome and physiologic GH deficiency, inflammatory cardiovascular indices and carotid IMT will be increased, indicating increased arteriosclerotic vascular disease. We will subsequently test the use of a novel strategy to restore physiologic GH levels and reduce inflammatory markers and IMT in this population, using a GH secretogogue shown to be safe in patients with diabetes and effective in other models of central obesity. Lay Description: This grant will study how commonly low GH level are seen and contribute to increased cardiac risk in patients with abdominal fat and whether increasing low GH levels will improve cardiac risk in this population. [unreadable] [unreadable] [unreadable] [unreadable]